The basis has grown from 75 operators to 86, and the curated feedstock behind them from 3,818,459 to 4,736,345 entries. The eleven additions are below, each drawn firing on real members of its own pools rather than shown as a SMARTS string.
The selection is deliberate rather than opportunistic. Nine of the eleven are bond constructions that became routine in kinase medicinal chemistry after the original work, and their absence meant whole regions of accessible chemistry could not be reached: no biaryl coupling, no triazole, no sulfonamide, no aryl amination. The tenth builds a heteroaromatic core in place rather than requiring it as a purchased fragment, and the eleventh is not a reaction at all.
| Basis | Operators | Feedstock entries |
|---|---|---|
| Original | 75 | 3,818,459 |
| 2026 | 86 | 4,736,345 |
Not a reaction. Admits any catalogue compound into a route unchanged, so a protocol can begin from a purchasable molecule rather than requiring a bond-forming first step. Its pool is the whole feedstock, which is why it is by far the largest.
[A,a:1]>>[A,a:1]Amine plus sulfonyl chloride. One of the most heavily used bond constructions in kinase medicinal chemistry and absent from the original basis.
[N;!H0:1][H].[S;$(S(=O)(=O)(Cl)[A,a]):2](=[O:3])(=[O:4])(Cl)[A,a:5]>>[N:1][S:2](=[O:3])(=[O:4])[A,a:5]Amine plus aldehyde to the secondary amine. The standard way to install a basic nitrogen with control over substitution.
[N;!H0:1][H].[C;$([C;!H0](=O)[A,a]):2](=[O:3])([A,a:4])[H]>>[N:1][C;!H0:2]([A,a:4])([H])[H]Aryl halide plus terminal alkyne. Introduces rigid linear linkers, which the 2005 basis had no route to.
[c:1][Br,I].[C;!H0:2]([H])#[C:3][A,a:4]>>[c:1][C:2]#[C:3][A,a:4]Terminal alkyne plus organic azide to the 1,4-triazole. Post-dates the original basis entirely and is now ubiquitous.
[C;!H0:1]#[C:2][A,a:3].[A,a:7][N:4]=[N+:5]=[N-:6]>>[n+0:4]1([A,a:7])[c:1][c:2]([A,a:3])[n+0:6][n+0:5]1Carboxylic acid plus alcohol.
[C;$(C(=O)[OH]):1](=[O:2])[OH].[O;!H0:3]([H])[C;!H0:4]>>[C:1](=[O:2])[O:3][C:4]Hydrazine plus 1,3-dicarbonyl. Builds the heteroaromatic core in one step rather than requiring it as a purchased fragment.
[A,a:8][N;!H0:1]([H])[N;!H0;!H1:2]([H])[H].[C;$(C(=O)[C;!H0;!H1]C=O):3](=O)[C;!H0;!H1:4]([H])[C;$(C(=O)):5]=O>>[n:1]1([A,a:8])[c:3][c:4][c:5][n:2]1Aryl halide plus arylboronic acid to the biaryl. The single most used C-C bond formation in the modern kinase literature.
[c:1][Br,I].[c:2]B([OH])[OH]>>[c:1][c:2]Aryl halide plus amine (Buchwald-Hartwig conditions).
[c:1][Br,I].[N;!H0:2][H]>>[c:1][N:2]Chloro-azine plus amine. The classic hinge-binder attachment in kinase inhibitors, exploiting activation by the ring nitrogen.
[c;$(c[n]):1][Cl].[N;!H0:2][H]>>[c:1][N:2]Alcohol plus alkyl halide.
[O;!H0:1]([H])[A,a:2].[C;!H0;$([C;!H0][Br,I,Cl]):3][Br,I,Cl]>>[A,a:2][O:1][C:3]Every operator is checked before use: that it fires on its own pools, that each reactant slot has feedstock, that no pool is empty, that no catalogue identifier is fabricated or blank, that the legacy operators load identical pools under the new basis, and that each new operator appears in the successor-compatibility map and is not isolated within it. The full suite is twelve checks and all must pass before a run starts.